FISCAL YEAR 2017
MOON SHOTS PROGRAM
TM
ANNUAL REPORT
Thank you for believing in our mission to end cancer. As we report back to you, our generous donors, in the fifth year of The University of Texas MD Anderson Cancer Center’s Moon Shots ProgramTM, you will notice two clear themes. First, and most important, we are achieving results. We have opened 180 clinical trials based on Moon ShotsTM-generated research, and the projects we initiated at the launch of this ambitious program are benefiting patients in our clinics as well as people in our communities. The Anderson Algorithm is improving prospects for women with ovarian cancer and is being replicated by medical centers across the world. Ray and the SunbeatablesTM is teaching more and more children the importance of sun safety. Our first Moon Shot-developed drug is in clinical testing. Our initial efforts are paying dividends thanks to you. Second, as you read through the report, you will notice many names and projects are repeated across various Moon Shots and platforms. Drs. Elizabeth Shpall and Katy Rezvani. Ibrutinib. IACS-10759. Natural killer cells. Bloodbased biomarkers. We have denoted these collaborations (with an icon,
,)
to demonstrate the incredible cross-pollination of ideas that remains a hallmark of the Moon Shots Program. Created through the vision of former MD Anderson president Ronald A. DePinho, M.D., in 2012, the program’s focus on team science means that teams working within one disease site share ideas with their colleagues in another. Our platforms further emphasize this teamscience approach, as you will read that basic science discoveries often apply to many types of cancer. Such openness also demonstrates the massive benefit your philanthropy has for our patients. A gift to the Institute for Applied Cancer Science can benefit patients with leukemia as well as pancreatic cancer. A gift to the immunotherapy platform supports nearly all of the 13 disease sites and the more than 100 clinical trials to which the platform contributes. A gift to the proteomics platform supports the development of early detection and diagnostic blood tests for lung, pancreatic and prostate cancers. All of this is possible because of you and your generosity. Your decision to support this unique effort is helping save lives and proving that progress against cancer doesn’t need to take decades. We can improve patient survival much faster through concentrated, team-oriented, well-supported science. Our Moon Shots teams thank you. And our patients, three of whom you’ll read about in this report, thank you. You had the foresight to believe that advancements against cancer could be accelerated. You had the generosity to support MD Anderson’s comprehensive approach to team science. And you had the optimism to know that a world free from cancer is possible. Thank you.
TABLE OF CONTENTS Cancer Prevention and Control.............................................................................................. 4 HPV-Related Cancers Moon Shot.......................................................................................... 6 Melanoma Moon Shot.............................................................................................................. 7 Institute for Applied Cancer Science..................................................................................... 8 Center for Co-Clinical Trials..................................................................................................... 9 AML-MDS Moon Shot.............................................................................................................. 11 Adoptive Cell Therapy............................................................................................................. 12 CLL Moon Shot......................................................................................................................... 13 B-Cell Lymphoma Moon Shot............................................................................................... 15 High-Risk Multiple Myeloma Moon Shot............................................................................ 16 Breast Cancer Moon Shot..................................................................................................... 19 Ovarian Cancer Moon Shot...................................................................................................20 APOLLO......................................................................................................................................22 Cancer Genomics Laboratory............................................................................................... 24 Proteomics................................................................................................................................ 26 Lung Cancer Moon Shot........................................................................................................ 27 Pancreatic Cancer Moon Shot..............................................................................................29 Prostate Cancer Moon Shot.................................................................................................. 31 Colorectal Cancer Moon Shot...............................................................................................32 ORBIT..........................................................................................................................................33 Immunotherapy.......................................................................................................................34 Glioblastoma Moon Shot.......................................................................................................36
CANCER PREVENTION AND CONTROL
Estimates based on a broad range of scientific evidence indicate that more than 50% of cancers can be prevented. The cancer prevention and control platform aims to accelerate the development, dissemination and amplification of evidence-based strategies, community services, policy interventions
Program Leaders: Ernest Hawk, M.D., M.P.H.,
and knowledge-targeting measurable reductions in
Mark Moreno, Michael T. Walsh Jr.
cancer incidence and mortality at a population level.
Lung Cancer Moon Shot
access to screening and treatment as well as
EndTobacco is a platform initiative focused on
improving education and training for providers. This
preventing and reducing cancer through evidence-
year, the team initiated projects in the Caribbean and
based policies, prevention and cessation services. As a
expanded projects in Mozambique and South Texas.
®
result of The University of Texas (UT) System Eliminate Tobacco Use initiative, all 14 system institutions are
Standard-of-Care Dissemination, BRCA
tobacco-free as of June 1, 2017. The initiative hosted
Through this project, the platform is improving
its second summit in April 2017 to share best practices
identification, genetic counseling and genetic testing
and discuss next steps as well as plan for expansion
uptake among a BRCA-mutation enriched population
efforts beyond the UT System. Cancer prevention
of patients with triple-negative breast cancer and
and control staff, working closely with MD Anderson’s
high-grade epithelial ovarian cancer and their close
Office of Governmental Relations, served as an
relatives at MD Anderson Physician Network locations.
educational resource to state and national partners on policy initiatives, such as Tobacco 21, a campaign
Project ECHO®
aimed at raising the minimum legal age for purchasing
Project ECHO (Extension for Community Healthcare
tobacco products to 21 years old. Additionally, the
Outcomes) is a capacity-building model that allows
EndTobacco program, in conjunction with
MD Anderson specialists to meet with and provide
MD Anderson’s Tobacco Treatment Program (TTP)
telementoring for advanced practice providers and
team, held over 70 tobacco cessation telementoring
physicians from rural and underserved areas in the
clinics for behavioral health professionals throughout
U.S, Latin America, Africa and other low-resource
Texas. With the continued collaboration with the TTP
settings. Primarily held through video conferencing,
staff, the cancer prevention and control platform team
sessions involve discussions of clinical guidelines and
successfully obtained a national accreditation that
best practices for management of select cancers,
trains health care professionals to become certified
cervical cancer prevention, tobacco treatment,
tobacco treatment specialists.
pathology, pharmacy operations and other related services, such as palliative care and survivorship.
HPV-Related Cancers Moon Shot
MD Anderson partnered with the ECHO Institute at
We are working to reduce the incidence and mortality
The University of New Mexico to become the first
of cervical cancer through targeted solutions and
oncology-focused Project ECHO Superhub in February
strategies in areas with a significant cervical cancer
2017, serving as a training and support site for other
burden in Texas, Latin America and sub-Saharan
organizations interested in developing Project ECHO
Africa. Through provider capacity building, affordable
programs with a focus on cancer. The first Project
technologies and health system strengthening, the
ECHO Superhub training took place in May 2017.
cancer prevention and control team is improving
4
Melanoma Moon Shot: MD Anderson’s Office of Governmental Relations, the Melanoma Moon ShotTM and the cancer prevention and control platform served as clinical and scientific resources to state legislators, clinical colleagues and other key stakeholders on tanning bed prohibition legislation. A recent study, conducted by MD Anderson, found that 81% of indoor tanning facilities complied with Texas’ state law that bans tanning for minors, underscoring the importance of this approach as a strategy for skin cancer prevention. To date, 17 states and the District of Columbia now have tanning bed prohibition legislation. The platform team also worked closely with the CATCH Global Foundation to disseminate Ray and the Sunbeatables™ — a sun safety curriculum developed by MD Anderson for preschoolers, kindergarteners and first-graders — to new schools across the country. In June, the digital version of the program was launched at www.sunbeatables.org, which allows any user with an internet connection to access this curriculum for free. Next year, the platform plans to partner with a leader in comprehensive education solutions to reach even more children.
Be Well Communities™
Pasadena Vibrant Community
The mission of Be Well Communities is to mobilize
The mission of the Pasadena Vibrant Community
communities to promote wellness and stop cancer
is to mobilize Pasadena, Texas, to promote health
To reduce cancer incidence, we must put knowledge about cancer prevention and control into action in people’s daily lives.
before it starts. The
and wellness in the community. The initiative unites
inaugural community
individuals, schools, workplaces, government agencies,
is Baytown, Texas, the
health care providers and policy makers to carry
third-largest city in
out community-led solutions that will make positive,
Harris County. Over
long-lasting changes in people’s health. Through this
the past year, the team
collaboration, MD Anderson will be impacting close
established a community-based steering committee
to 33% of the Pasadena community through diet and
to develop a community action plan to deliver
physical activity interventions.
evidence-based interventions in partnership with key stakeholders. Through the community action
Thanks to your generous support, the cancer
plan, close to 66% of the Baytown community will be
prevention and control platform is positioned to help
impacted through education, programs and health
drastically reduce incidences of cancer around the
services.
world. Thank you.
5
HPV-RELATED CANCERS MOON SHOT Program Leaders: Cathy Eng, M.D.; Lois Ramondetta, M.D.; Erich Sturgis, M.D., M.P.H.; Kathleen Schmeler, M.D.
Cathy Eng, M.D., professor of Gastrointestinal Medical Oncology Thanks to your generosity, the HPV-Related Cancers
We are making great strides in the laboratory, delving
Moon Shot™ is working to eliminate HPV-related
into the secrets of HPV cell lines and HPV-related
cancers in the future through prevention efforts
cancers. Cathy Eng, M.D., led a multi-institutional study
including vaccination and screening, while seeking
of the immunotherapy drug, nivolumab, for patients
more effective, less toxic treatments for patients
with anal cancer. In this study, nivolumab was used to
who are diagnosed with these cancers now. Your gift
catalyze the patients’ own T cells to fight metastatic
has allowed us to develop programs to increase HPV
anal cancer resistant to other therapies. Some cancer
vaccination rates in the United States and globally,
cells, such as advanced anal cancer, disrupt normal
to improve access to cervical cancer screening in
T cell immune function by binding to a receptor on
low-resource areas and to activate a first-of-its-kind
the T cells known as programmed death-1 (PD-1).
study to identify effective screening approaches for
This halts T cell function and prevents the T cells
noncervical HPV-related cancers. In addition, we
from killing the cancer cells. Nivolumab targets PD-1
are finding novel effective treatments for those with
and related proteins, releasing the T cells to kill more
HPV-related cancers, bringing discoveries from the
cancer cells. The study demonstrated an impressive
laboratory to the clinic across several disease sites.
response rate and was published in Lancet Oncology.
With your support, we are training health care
We are incredibly grateful for donors to the HPV-
professionals on proven methods to increase HPV
Related Cancers Moon Shot, who make our efforts to
vaccination rates in their clinics. Our approach
reduce the suffering caused by this disease possible.
distinguishes itself from other HPV vaccination education resources by combining provider education with quality improvement practices, such as setting up a standard process by which clinics remind patients to return for vaccination.
6
Early results show improved HPV vaccination rates in key populations across Texas, and the program is expanding nationwide through the MD Anderson Cancer Network.
“These exciting results open a whole new field of opportunity to use the microbiome to potentially cure patients of cancer.” — Jennifer Wargo, M.D.
MELANOMA MOON SHOT
Program Leaders: Jeffrey Gershenwald, M.D.; Michael Davies, M.D., Ph.D.; Jennifer Wargo, M.D.
With the development of more effective therapeutic
to immunotherapy, the first study of its type to look at
strategies, and thanks to the generosity of our donors,
this relationship. Using gut microbiome biospecimens
the Melanoma Moon Shot™ opened the first clinical
(stool) collected from patients, Dr. Wargo and her team
trial, led by Rodabe Amaria, M.D., and Melanoma
identified differences in the composition and diversity
Moon Shot co-leader Jennifer Wargo, M.D., evaluating
of the gut microbiome in patients that responded
neoadjuvant (presurgical) immunotherapies. Patients
to PD-1-directed therapy versus nonresponders.
are randomized to either a single agent presurgical
They learned that
regimen of nivolumab (standard of care for patients
those who responded
whose cancer cannot be removed by surgery or
better to anti-PD-1
that has metastasized) or a presurgical combination
immune checkpoint
therapy of nivolumab and the immunotherapy,
blockade therapy had
ipilimumab. In addition, our team is partnering with
a greater diversity
the immunotherapy and Cancer Genomics Laboratory
of bacteria types in
platforms to perform deep analyses of tissue acquired
their microbiomes,
from patients participating in these studies in the hopes
and those who responded better also had increased
of identifying mechanisms of response and resistance,
abundance of the Ruminococcaceae family of bacteria.
The potential to improve immunotherapy response by changing the composition of the gut microbiome is particularly exciting since it involves simple, nontoxic interventions such as altering one’s diet and taking probiotics.
further personalizing future treatment strategies. None of these studies would be possible without the Another exciting project involves an examination
unwavering support of our donors. We are grateful for
of the role of the gut microbiome — the collective
your generosity.
population of microorganisms — in patient responses
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INSTITUTE FOR APPLIED CANCER SCIENCE Program Leader: Philip Jones, Ph.D.
The Institute for Applied Cancer Science (IACS)
Marina Konopleva, M.D., Ph.D., professor of Leukemia
was established in 2011 with the ambitious goal of Institute for Applied Cancer Science
advancing its first novel small molecule therapy into clinical testing within five years, and then producing a steady stream of subsequent clinical candidates that move into clinical trials. Now, in 2017, the IACS platform, in close collaboration with the translational biology capabilities of the Center for Co-Clinical Trials (CCCT)
IACS-10759
Center for Co-Clinical Trials
platform, is delivering on its promise thanks to the support of our generous donors. We have produced an exciting project portfolio with multiple agents expected
AML-MDS Moon Shot
to enter clinical testing in 2018. This momentum underscores the mission of IACS — to bring impactful therapies to cancer patients through bench-to-bedside drug development.
Pancreatic Cancer Moon Shot More clinical studies are opening to enroll melanoma,
Our most advanced project, IACS-10759, entered clinical
pancreatic and breast cancer patients because a
trials this year for safety and efficacy studies in patients
metabolic starvation approach can be applied to other
with relapsed/refractory acute myeloid leukemia (AML).
malignancies.
IACS-10759 is a novel drug targeting cancer cells’
8
mitochondria, the tiny cellular organelles that
Several programs are following closely on the heels of
produce metabolic energy. Cancer cells require a lot
IACS-10759. Over the past year, a wealth of preclinical
of energy to constantly replicate and grow, and several
data has been generated through cooperation
types of cancers depend on mitochondria for energy.
among IACS, CCCT and MD Anderson clinicians to
Targeting mitochondria in these cancers is essentially
support clinical trials for a second IACS-developed
draining the cancer cells’ batteries to starve them.
small molecule. This drug candidate, IACS-06274,
The clinical trial, led by Marina Konopleva, M.D., Ph.D.,
inhibits glutaminase, another enzyme critical for
professor of Leukemia, and Naval Daver, M.D., associate
energy production and the supply of cellular building
professor of Leukemia, is the result of a partnership with
blocks. Like IACS-10759, this drug also drains cancer
the AML-MDS Moon Shot™ and a $3.5 million grant from
cells of an essential energy source, but it targets a
the Leukemia and Lymphoma Society. The drug has
metabolic process rather than mitochondria. The drug
shown to be well tolerated in the patients treated to date,
is undergoing toxicology studies and clinical supplies
effectively shutting down the mitochondria in AML cells.
manufacturing in accordance with FDA regulations for
first-in-human clinical evaluations. Rigorous preclinical
Since February 2017, this collaboration has driven two immuno-oncology projects toward the clinic, and both have potential to be tested in patients in 2018.
testing is demonstrating how this potential drug can modulate the immune system to further affect the cancer cell’s biology. It is on track to enter clinical evaluation in summer 2018 in studies with the Lung Cancer Moon Shot
TM
Another project targets a protein frequently mutated
and Ovarian Cancer Moon Shot . TM
in both hematological malignancies and solid tumors that also acts as a resistance mechanism in a number of
Strategic partnerships with pharmaceutical companies
commonly used targeted therapies. The IACS and CCCT
will be essential in bringing our drugs to more cancer
teams have discovered an innovative approach to shut
patients. The IACS team has advanced two projects with
down signaling by this oncogene and are advancing
TESARO Inc., an oncology-focused biopharmaceutical
novel therapies into late-stage preclinical testing and,
company.
hopefully, in clinical trials in 2018.
CENTER FOR CO-CLINICAL TRIALS
The CCCT collaborates with Moon Shots teams and the Institute for Applied Cancer Science (IACS) — MD Anderson’s small molecule drug discovery platform — to evaluate novel therapeutics in sophisticated preclinical models. In addition to safety and efficacy studies, the CCCT performs biological
Program Leaders: Joseph Marszalek, Ph.D.;
studies to determine which patients may benefit from
Tim Heffernan, Ph.D.
therapy and develops mechanisms to identify these patients.
Despite recent notable successes in
In 2016, our collaborative work with IACS yielded the
oncology drug development, only 5% of
first entry of a novel therapeutic from MD Anderson
experimental cancer drugs prove effective
into a clinical study. The CCCT collaborated with
when tested in clinical trials. One factor
investigators from eight Moon Shots to accelerate
contributing to this high failure rate is the
the translation of IACS-10759, an inhibitor of cancer
advancement of drugs into clinical testing
energetics, and defined patient subpopulations
without sufficient biological insight to
for clinical evaluation. Through extensive preclinical
guide patient selection. This is a costly
testing, the CCCT and our clinical collaborators designed
and inefficient approach that exposes
this first-in-human study in patients with acute myeloid
an overwhelming majority of patients to
leukemia, and we initiated an additional Phase I study in
futile therapies. To address this problem,
patients with pancreatic and breast cancers, as well as
MD Anderson established the Center for
melanoma in the third quarter of 2017.
Co-Clinical Trials (CCCT), a Moon Shots
TM
platform with an unprecedented focus on
Our preclinical activities also have supported the
translational biology. The goal of the center
development of the broader IACS drug discovery
is to provide the world-class faculty of
portfolio, which is poised to advance five novel
MD Anderson the necessary insights to
therapeutic modalities into the clinic by the end
deliver transformative medicines to our
of 2018. This includes IACS-06274, an inhibitor of
patients.
glutaminase, which is a critical metabolic enzyme
9
that fuels tumor growth. Through a comprehensive
that may enhance the activity of BTK inhibitors. In
translational effort, we have identified biomarkers
collaboration with the Melanoma Moon ShotTM and
designed to predict sensitivity to IACS-06274 in
Lung Cancer Moon ShotTM, we have initiated preclinical
patients diagnosed with non-small cell lung cancer
trials to analyze how targeted therapies may be
or high-grade serous ovarian cancer. The CCCT is
used to enhance the activity of immunotherapies.
currently executing FDA-mandated studies to support
In addition, the CCCT has completed a series of
the filing of an Investigational New Drug application for
preclinical studies with the Breast Cancer Moon ShotTM
permission to initiate Phase I clinical studies in 2018.
to identify targeted therapies that would enhance the activity of PARP inhibitors in triple-negative breast
In addition to evaluating novel therapeutics, the CCCT collaborates with Moon Shots to test hypotheses that may reposition or enhance the impact of cancer drugs.
cancer. With your generous support, these efforts have helped prioritize new effective therapeutic combinations that are progressing toward clinical trials conducted by Moon Shots leadership.
Recent efforts include a partnership with the CLL Moon ShotTM team to evaluate drug combinations
Jeffrey Kovacs, Ph.D., institute senior research scientist in the CCCT
10
AML-MDS MOON SHOT Program Leaders: Guillermo Garcia-Manero, M.D.; Hagop Kantarjian, M.D.
The Moon Shots ProgramTM has developed multiple translational research initiatives significantly impacting
Investigators led by Richard Champlin, M.D.,
our understanding of myelodysplastic syndromes
have developed new stem cell transplant
(MDS) and acute myeloid leukemia (AML). Our effort
technologies using and targeting natural killer
is collaborative, bringing together investigators in
(NK) cells to improve transplant outcomes.
Leukemia and Stem Cell Transplantation along with
Examples include the use of ex vivo expanded
those from several platforms. And your generous
NK cells (cells that have been multiplied in
support has made this progress possible.
the lab before infusion) that are now being tested in Phase II clinical trials to enhance
One of the most significant discoveries in the
the graft-versus-leukemia effect of stem cell
biological sciences over the past two years has
transplantation. In addition, investigators
been the identification of mutations in the blood of
are working on boosting the efficacy of NK
some patients without disease. This phenomenon
cells by targeting a specific leukemia antigen
is known as clonal hematopoiesis or CHIP. Initial
known as PR1.
data indicated that CHIP is associated with an increased risk of developing leukemia. Investigators at MD Anderson, with the support of the Cancer
related leukemia in patients with CHIP.
Genomics Laboratory, have taken this observation forward by demonstrating that nearly 75% of patients
A significant collaboration between our team and IACS
with therapy-related leukemia have evidence of CHIP.
resulted in the development of the agent IACS-10759.
Knowing that CHIP can help identify patients at risk for therapy-related leukemia is transformative, as it allows us to develop preventive strategies. This concept — unimaginable just a couple of years ago — is already being applied to our patients at MD Anderson.
Therapy-related
IACS and the AML-MDS Moon ShotTM team designed,
leukemia is very
synthesized and tested more than 800 compounds
aggressive with a
through this process to arrive at IACS-10759. In a
poor prognosis and
Phase I clinical trial, seven patients already have
occurs in patients
been treated without significant toxicity.
who were treated with chemotherapy
Finally, a new project initiated in the last year, led
or radiation for
by Michael Andreeff, MD., Ph.D., focuses on the
lymphoma, myeloma
eradication of residual leukemic stem cells in patients
or solid tumors. In collaboration with the High-Risk
in remission after successful chemotherapy. This
Multiple Myeloma Moon ShotTM and B-Cell Lymphoma
program already has proven that it is possible to
Moon Shot™, we are studying the incidence of CHIP in
isolate these residual cells in patients, leading the way
patients receiving autologous stem cell transplantation
to newer curative strategies for patients with AML.
(in which patients’ own cells are treated and infused back into them). This group is at highest risk of
We are very proud of this effort, achieved only with
developing therapy-related leukemia. In parallel,
your support. We believe that this Moon Shot is
investigators led by Guillermo Garcia-Manero, M.D.,
significantly contributing to the continuous cure of
are designing clinical trials with low doses of epigenetic
patients with AML and MDS.
therapy and immunotherapy to prevent therapy11
ADOPTIVE CELL THERAPY Program Leaders: Elizabeth Shpall, M.D., Cassian Yee, M.D.
The adoptive cell therapy platform programs immune
preclinical evidence that demonstrates the death of
cells to recognize and attack cancer. We are excited
leukemia cells upon infusion. Your support has made
about a number of projects, including the development
this exciting work possible.
of novel cord blood-derived natural killer (NK) cells for patients enrolled in trials from the AML-MDS Moon
In collaboration with the CLL Moon Shot, we have
Shot , High-Risk Multiple Myeloma Moon Shot
designed cord blood NK cells carrying the CAR
TM
With technology developed right here at MD Anderson, we have multiplied NK cells in the lab and — for the first time ever — infused them back into patients, providing a far larger dose of tumor-killing NK cells.
TM
and
Chronic Lymphocytic
targeting the CD19 protein, a strategy designed to
Leukemia (CLL) Moon
make the NK cells even more potent and effective
ShotTM. Chimeric
at eliminating CD19-positive cancers. Additionally,
antigen receptor
the platform is producing two adoptive cell therapy
(CAR) T cell therapy
products for the Melanoma Moon Shot™: tumor-
involves engineering
infiltrating lymphocytes (TILs) and endogenous T cells
T cells to recognize
(ETC). Patients with metastatic melanoma will receive
specific antigens
intravenous TILs in conjunction with the check-point
the cancer cells express. We then expand them and
inhibitor, pembrolizumab, while personalized ETC will be
infuse them back into the patient. While effective, this
used to treat uveal melanoma with liver metastases.
approach has drawbacks, including the fact that the T cells have to come from the patient to avoid the risk
Another exciting project in the validation phase will use
of graft-versus-host disease. NK cells from a normal
allogeneic (taken from a donor) bone marrow-derived
umbilical cord blood donor, however, can be engineered
mesenchymal stem cells loaded with the tumor-
to express CARs, expanded and then stored for use
selective oncolytic adenovirus, DNX-2401, for patients
in virtually any patient. This off-the-shelf approach
with recurrent glioblastoma, a disease for which few
eliminates not only the need for creating a new batch
therapeutic options exist.
of tumor-targeting cells for each patient, but also the
12
weeks-long wait that goes with doing so. The cells even
None of the work we are able to do to support the
include a “suicide gene” that allows us to eliminate them
Moon Shots ProgramTM would be possible without your
if they are found to cause substantial toxicity. We have
support. Thank you.
Adoptive Cell Therapy
CARmodified NK cells
CLL Moon Shot
B-Cell Lymphoma Moon Shot AML-MDS Moon Shot
Left: Katy Rezvani, M.D., Ph.D., and Elizabeth Shpall, M.D.
CLL MOON SHOT Program Leaders: Michael Keating, M.B., B.S.; William Plunkett, Ph.D.; William Wierda, M.D., Ph.D. We are excited to share the advances made during the
Ibrutinib has now been adopted as frontline therapy
past year in the Chronic Lymphocytic Leukemia (CLL)
for most CLL patients. Yet there remain curative
Moon Shot . In last year’s report, we detailed our
limitations to this breakthrough drug, and prolonged
involvement in the breakthrough therapies venetoclax
use of it can be expensive, costing more than
and ibrutinib. Thanks to your continued support,
$130,000 per year. For many patients it is not feasible
we were able to build upon our discoveries and
— physically or financially — to continue on this
experiences to push the envelope further.
therapy. To better serve CLL patients, Varsha Gandhi,
TM
Ph.D., professor of Experimental Therapeutics, Immunotherapy has been a hallmark of our program
conducted studies to determine whether lowering
since inception, and all the hard work is beginning
the dose of ibrutinib would be safe for patients while
to pay off. Katy Rezvani, M.D., Ph.D., professor of
still being effective. Based on her initial investigations
Stem Cell Transplantation and Cellular Therapy,
in the laboratory and a pilot clinical trial, we believe
helped to develop a novel therapy that uses NK
that a lower dose of ibrutinib is optimal and can
cells modified by CARs to target and kill CLL cells.
achieve the necessary therapeutic effect for patients.
The CAR NK cell program has reached clinical trial
We will be launching a Phase II study to confirm these
status and we are beginning to enroll patients in a
findings. Ultimately, lower doses of ibrutinib will mean
first-in-human study. We are sincerely grateful that
less toxicity and lower costs — a win-win for patients
your generosity has led us to this significant milestone,
and providers!
which has filled us with hope for a potential curative therapy for our patients. 13
Our team is also devising another strategy to
just three months, the patient is showing a complete
overcome ibrutinib’s limitations. One of the
response on his PET imaging and continues on the
immunotherapy studies we initiated last year
clinical trial.
combined ibrutinib with nivolumab. Although it appeared at first to have minimal effect on the disease, we discovered that this unique combination significantly benefits patients with Richter’s Transformation — a syndrome in which
This kind of response for Richter’s Transformation patients was nearly unheard of before this study — and there are many more stories like this.
CLL transforms to a highly aggressive form of B-cell lymphoma associated with poor prognosis. One of
This is an exciting time for the CLL Moon Shot as we
the patients on the trial had already been treated
see years of effort come to fruition for the benefit
with chemotherapy and ibrutinib for more than two
of our patients. Thanks to you, and other generous
years before developing Richter’s Transformation. His
donors like you, we are moving closer to eradicating
oncologist recommended our clinical trial combining
CLL once and for all.
ibrutinib and nivolumab, led by Nitin Jain, M.D. After
Betty Lamothe, Ph.D., assistant professor of Experimental Therapeutics, in the lab
14
B-CELL LYMPHOMA MOON SHOT Program Leaders: Richard Champlin, M.D.; Michael Wang, M.D.
With support from our donors, the B-Cell Lymphoma
Transplantation and Cellular Therapy, and fellow Moon
Moon Shot
Shot team members have addressed this problem
TM
team has continued to address problems
that stand in the way of better outcomes for our
with CAR T cells that are primed to recognize and kill
patients.
lymphoma. A multicenter clinical trial of CAR-modified T cells in relapsed B-cell lymphoma (mostly DLBCL),
One of the biggest problems we face is how to prevent
led by Sattva Neelapu, M.D., associate professor of
lymphoma from returning after initial therapy, at which
Lymphoma/Myeloma, produced stable complete
point it often shows resistance to further treatments.
remissions in about 40% of patients, many of whom
Up-front intensive therapy — which is harsh but
had run out of treatment options. Based on these
effective — offers the best chance for mantle cell
trial results, the FDA approved this type of CAR T cell
lymphoma (MCL) cure.
therapy in October of 2017, and combination trials using CAR T cells are underway or planned.
Working with the Cancer Genomics Laboratory, we successfully identified a predictor of how patients respond to treatment based on the genetic make-up of their tumors.
One limitation of CAR T cells is that they are not yet available for all patients who need them, partly because they are made from the patient’s own T cells
This will allow us to stay one step ahead of the
in a somewhat time-consuming process. In contrast,
disease and turn immediately to more effective
natural killer (NK) cells do not need to be patient-
options if one therapy begins to fail. Michael Wang,
specific and are available “off-the-shelf” from banked
M.D., professor of Lymphoma/Myeloma, designed
umbilical cord blood. Katy Rezvani, M.D., Ph.D., and
a trial to add the targeted agent ibrutinib, which
Elizabeth Shpall, M.D., have shown that unmodified
inhibits specific features of lymphoma cells, to
NK cells have natural antitumor effects and are safe to
combination chemotherapy. Using a “window” trial
give to patients. They also have confirmed in mouse
design that administers ibrutinib (and rituximab) prior
models that CAR-modified NK cells derived from cord
to chemotherapy, Dr. Wang’s team achieved a 100%
blood are longer lasting and have stronger cancer-
rate of complete remission in previously untreated
killing ability. In collaboration with the adoptive
MCL patients. This result alone, if confirmed in
cell therapy platform, we have recently launched
larger studies, will increase the efficacy of frontline
MD Anderson’s first-in-human clinical trial of
MCL treatment while reducing its toxicity and could
cord blood-derived CAR NK cells for lymphoma.
potentially provide the basis for future testing of
Additionally, Jeffrey Molldrem, M.D., is identifying new
combinations that are entirely chemotherapy-free.
antigen targets for effective immunotherapy using monoclonal antibodies or antigen-specific T cells.
We also seek to improve outcomes for the nearly 10,000 new patients each year in the U.S. who relapse
Our team deeply appreciates our donors’ generosity,
after initial therapy for diffuse large B-cell lymphoma
which has made our research efforts and achievements
(DLBCL), a common but aggressive form of the disease.
possible and will profoundly impact the lives of those
Current options are highly toxic and less than 25%
saved. Working together, we will reach the ultimate goal
curative. Richard Champlin, M.D., chair of Stem Cell
of doubling the cure rate of B-cell lymphoma.
15
HIGH-RISK MULTIPLE MYELOMA MOON SHOT Program Leaders: Robert Orlowski, M.D., Ph.D.; Eric Davis, M.D.; Donald Berry, Ph.D.
Multiple myeloma (MM) is the second most commonly
in remission; this is the first report of any response
diagnosed hematologic malignancy, with the rate of
to a single-agent immunotherapy in smoldering MM.
new cases expected to grow by almost 60% from
Even more encouraging, myeloma cells from this
2010 to 2030, due in part to our aging population.
particular patient harbored one of the most serious
While current therapies for multiple myeloma are not
genetic abnormalities, del17p, which is associated with
curative, they can extend survival for many years,
poor prognosis. Overall survival of patients with this
meaning virtually all patients will develop and succumb
abnormality after progressing to symptomatic MM is
to relapsed/refractory multiple myeloma.
only two to three years. All but one of the remaining patients on this trial have stable disease.
In view of the difficulty and growing size of the problem posed by multiple myeloma, the High-
In the second trial, we are targeting a specific
Risk Multiple Myeloma Moon Shot™ is pursuing a
molecule, CD38, on the surface of myeloma cells with
bold solution: to cure the disease before it evolves
an antibody called isatuximab, intended to elicit an
into the symptomatic stage. Multiple myeloma has
anti-myeloma immune response. This trial opened in
well-defined, easily detectable precursor states
February 2017, and the first patient showed a partial
— monoclonal gammopathy of undetermined
response after just one round of therapy.
significance, and smoldering multiple myeloma — both of which carry a lifetime risk of progression to
In collaboration with Moon ShotsTM platforms,
symptomatic MM. However, even high-risk patients
characterizations of myeloma and immune cells from
are currently not treated, largely because toxicities
patients on these trials will help us understand the
associated with available chemotherapies outweigh
differences in their responses, and ultimately will
any benefit.
help us in the design and patient selection of future clinical trials.
But we now have new, less toxic immunotherapies that have given us an opportunity to intervene with
These early results convince us that we are on the
patients early to improve their long-term outcomes.
right track. With your support, we are moving toward
Our Moon ShotTM has opened two clinical trials to show
launching larger trials of immunotherapy in precursor
that novel immunotherapies can delay or prevent
states of MM, improving our analysis of samples and
intermediate- and high-risk patients from developing
better understanding how the immune system can
symptomatic MM.
prevent progression to symptomatic disease.
Progression from smoldering MM to symptomatic MM may be caused by exhaustion and/or inhibition of the patient’s immune system by myeloma cells. One of our trials uses pembrolizumab, an antibody designed to wake up or restore the patient’s immune system. One patient achieved a complete response after just three rounds of pembrolizumab and remains
16
”The very best way to help our patients is to cure myeloma before it ever evolves into the symptomatic phase. These trials show the promise of doing just that.” — Robert Orlowski, M.D., Ph.D.
“I'm not as afraid of a possible relapse as I once was, largely due to new drug therapies for relapsed and refractory disease.” — Karen Fore, multiple myeloma survivor
My Multiple Myeloma Moon Shot by Karen Fore
In June 2010, I was diagnosed with multiple
I'm not as afraid of a possible relapse as I once
myeloma, a blood cancer that attacks the bone
was, largely due to new drug therapies for relapsed
marrow, bones and kidneys. I'd never heard of
and refractory disease. Knowledge is power;
it, even though I'd worked in the medical field
therefore, I set out to keep up with the most current
for decades. I began chemotherapy almost
developments for multiple myeloma treatment. The
immediately, with little results. We tried a second
progress is extremely exciting!
line of treatment and it also failed. Eventually, I was enrolled in a clinical trial that controlled the
I was thrilled that multiple myeloma was chosen
disease enough to proceed to a stem cell transplant.
to be part of the Moon Shots Program™. They're
Thankfully, 18 months later, I achieved a complete
researching how the body can use its own immune
response and have been blessed to maintain this
system and special killer cells to eradicate the
remission to this day.
myeloma cells from the body — in other words, a cure! There's hope for those diagnosed with multiple
This is a disease that currently has no cure, however,
myeloma. With the intensive research being done
and can recur at any time. I hold my breath with
through the Moon Shots Program, I believe this cure
each follow-up visit hoping that I'm still in remission.
will come in my lifetime.
This story originally appeared on Cancerwise, MD Anderson’s blog for patients, caregivers and survivors: www.cancerwise.org.
17
Breast cancer cells (above) are the result of mutations in the tumorsuppressing gene, BRCA, in 5 to 10% of all breast cancer patients. Moon Shot investigators are using targeted therapies to attack BRCA-associated tumors.
18
BREAST CANCER MOON SHOT
Program Leaders: Junjie Chen, Ph.D.; Stacy Moulder, M.D.
Precision medicine is the use of modern
Jennifer Litton, M.D., and Banu Arun, M.D., lead the
molecular testing and/or imaging to identify and
Breast Cancer Moon Shot’s Uncommon and Rare
target abnormalities in cancer cells that possess
Breast Cancer Initiative, currently testing targeted
characteristics that make them vulnerable to
therapies in select patient populations. Their exciting
therapeutic attack. Recently, we have improved breast
work has resulted in complete disappearances of
cancer cure rates due, in part, to our ability to identify
cancer within the breast and surrounding lymph
and treat newly diagnosed patients at high risk of
nodes in patients with BRCA-associated tumors
having small, undetectable deposits of cancer cells
treated with targeted therapy before surgery.
in their bodies that will develop into tumors if left untreated. A goal of the newly formed Breast Cancer
When chemotherapy alone or combined with targeted
Moon Shot
therapies causes a complete response in the breast,
TM
is to use precision medicine to cure
breast cancer.
the prognosis is exceptionally good because the drug also is likely killing tumor cells elsewhere in the body
The innovative ARTEMIS trial studies triple-negative
that are too small to detect.
breast cancer, an especially aggressive form of breast cancer, for which no common targeted therapy exists. In less than two years, this trial has molecularly profiled nearly 200 individual triplenegative cancers, generating information that will best allow us to predict response based on specific genetic profiles. Approximately 30 of these tumors have been identified as unresponsive to chemotherapy,
“The early finding that a single targeted drug can cause a complete, durable response if used in the right patient population is especially promising and suggests that one day, patients can avoid chemotherapy altogether.” — Jennifer Litton, M.D.
indicating a 40 to 80% risk of death within three years
The Breast Cancer Moon Shot also supports unique
of diagnosis. We have enrolled nearly all of these
hypothesis-driven research into the causes of drug
patients with tumors unresponsive to chemotherapy
resistance, which helps us to develop promising new
into clinical trials with targeted therapies selected
treatment strategies. Helen Piwnica-Worms, Ph.D., uses
based upon the molecular profiling of their tumor.
tumor tissue from clinical trials in triple-negative breast
The results to date have been promising. We also are
cancer and BRCA-associated cancers and implants
testing exciting new imaging techniques to identify
them into mice to create patient-derived xenograft
cancers that are resistant to chemotherapy because
(PDX) models. Researchers then perform molecular
of poor blood supply or the presence of “drug pumps”
characterizations on both patient samples and PDXs
within cancer cells that remove chemotherapy before
pre- and post-therapy; the differences we discover
it has a chance to work.
help us to determine causes of resistance, leading to promising new treatment strategies that we can test in
An important component of breast cancer is its
PDXs prior to entering clinical trials in patients.
nature as a diverse disease that can be grouped into numerous subtypes, each of which requires a different
Your support has a multiplier effect, as it has provided
targeted therapy to cure patients. Because of our
infrastructure and preliminary data for successful
substantial patient volume and faculty expertise, we
grant applications that have procured over
are optimally positioned to develop targeted therapy
$13 million in funding for the institution.
strategies in this age of precision medicine.
Thank you for making our work possible.
19
OVARIAN CANCER MOON SHOT Program Leaders: Anil Sood, M.D.; Gordon Mills, M.D., Ph.D.; Shannon Westin, M.D.
In 2010, Diane Sarver was diagnosed with stage IV
to chemotherapy altogether. Over the past few years,
ovarian cancer. One round of chemotherapy put
with the support of our committed donors, the Ovarian
Diane into remission, but two-and-a-half years later
Cancer Moon Shot team has launched several clinical
she would have her first ovarian cancer recurrence;
trials to address recurrent, therapy-resistant tumors.
she would go on to have two more recurrences. Diane
The team asks: Can we use a personalized approach to
knew it was time to seek other options and came to
chemotherapy for our patients with recurrent disease
MD Anderson. She enrolled in a clinical trial aimed at
in an effort to increase durable remission?
treating recurrent disease through the Ovarian Cancer Moon Shot™. This year marks Diane’s third year on the
The program has developed a portfolio of clinical trials
trial and second year in remission.
to better understand the DNA of ovarian cancer cells. Currently, the Ovarian Cancer Moon Shot includes
20
One of the Ovarian Cancer Moon Shot’s first
more than 15 clinical trials. With generous donor
accomplishments was the development of the
support, we have taken exciting benchmark data
Anderson Algorithm, a personalized surgical approach
and translated the findings into the clinic. One of the
to cancer therapy. This protocol substantially increases
goals is to understand the mechanisms that help a
the frequency of complete visible tumor removal,
cancer cell repair its damaged DNA when treated with
which has been shown to increase patient survival,
chemotherapy. If we determine what helps the cancer
in women undergoing upfront debulking surgery.
cell thrive, we can target that element of resistance
While the algorithm is a groundbreaking approach
to destroy the cancer cell permanently. As part of
to frontline therapy, ovarian cancer is a disease that
our ongoing trials, we obtain pre- and post-treatment
frequently returns and eventually becomes resistant
biopsies to elucidate resistance mechanisms.
Diane Sarver, ovarian cancer survivor
Our work has shed light on an enzyme known as
Even further, as a companion to our PARP and related
PARP, which helps cancer cells by repairing DNA when
clinical trials, we have implemented patient-reported
it is damaged by chemotherapy. Our work also has
outcomes measurement tools to identify patients who
explored how to “re-sensitize” tumors that evolve to
may be at risk for side effects and less positive clinical
By focusing on making an already available drug more effective, we hope to increase the number of therapeutic options available for our patients.
resist PARP inhibitors,
outcomes.
and we have developed clinical trials for patients
MD Anderson’s Moon Shots Program™ demonstrates
who recur after PARP
our commitment to innovative research toward
inhibitor treatment.
eradicating cancer. This would not be possible without the generous support of our donors, and we take
Diane is a clinical trial patient on one of our PARP
this opportunity to graciously thank you for your
inhibitors. Thankfully, her story of survivorship is not
partnership in Making Cancer History ®.
unique. Implemented in 2014, the trial has enrolled 42 ovarian cancer patients. Preliminary analysis of the data demonstrates the drug combination is well tolerated and shows activity against tumor cell growth. We are pleased to report other clinical trials in our portfolio are proving to be just as effective in the fight to prevent ovarian cancer recurrence.
“A clinical trial can be life-changing and life-sustaining. Gain knowledge, ask questions and learn to become your own best advocate.” — Diane Sarver, CancerWise, April 2017
21
APOLLO Program Leaders: Andrew Futreal, Ph.D.; Ignacio Wistuba, M.D.
The Adaptive Patient-Oriented Longitudinal Learning and Optimization (APOLLO) platform of MD Anderson’s Moon Shots Program™ is aimed at the standardized collection of highquality research specimens before, during and after a patient’s treatment. By providing critical phenotype data paired with patient clinical data across cancer types, APOLLO accelerates discoveries and practice-changing patient outcomes. Moon Shot™ teams and other interested collaborators have successfully collected longitudinal patient samples thanks to a universal banking consent form that allows APOLLO to study high-interest patient clinical trials. APOLLO is designed to make advanced cancers more predictable and easier to defeat by focusing on the malignancy’s relentless ability to evolve and survive in response to treatment. APOLLO is powered by the expert sequencing capabilities and comprehensive molecular analyses of the Cancer Genomics Laboratory. The platform offers a paradigm-changing approach that accelerates the development of new methods based on scientific discoveries. Thanks to generous donor support, in October 2016, APOLLO expanded the list of projects for which it is collecting biospecimens beyond the original pilot projects. A novel immunotherapy clinical trial for stage IV metastatic melanoma patients, for example, demonstrates how APOLLO is enabling the kind of comprehensive analysis of patient samples that is becoming the gold standard of cancer care. Nancy Pinkston, melanoma
22
survivor, benefits from APOLLO's
The trial involves pre- and post-surgical
comprehensive surveillance approach.
treatment with a form of immunotherapy —
pioneered by immunotherapy platform leader, James
drug predicted which patients would respond. Pre-
Allison, Ph.D. — called immune checkpoint blockade,
treatment biopsies, however, didn’t find predictive
which frees the immune system to attack cancer,
genomic or immune biomarkers.
rather than attack cancer directly. Andrew Futreal, Ph.D., co-leader of APOLLO and the Nancy Pinkston joined the trial after a relapse
Moon Shots ProgramTM, knows that finding predictive
of her melanoma. She received four rounds of
biomarkers in pre-treatment biopsies is the Holy Grail,
immunotherapy (nivoumab) and then underwent
but he believes that pre-treatment and early on-
surgery in May 2017. Following surgery, Nancy got the
treatment biopsies might be a winning combination.
good news from Jennifer Wargo, M.D., co-leader of the Melanoma Moon Shot and associate professor
“We don’t take one CT scan initially and then use
of Genomic Medicine and Surgical Oncology: “All she
that same scan to assess how well treatment is
found at surgery was dead tissue and the biopsy
working three months later,” notes Dr. Futreal. “We
confirmed the good news — no evidence of disease.”
take a new scan.”
Clinical trial participants like Nancy are helping
A cancer patient generally undergoes a biopsy before
Dr. Wargo and her colleagues address a vital question:
starting treatment. After that, standard practice is to
Why do immunotherapy drugs work well for some
track the tumor’s progression using CT or MRI scans
patients, like Nancy, and briefly or not at all for others?
for size and volume and PET scans for metabolic activity. The APOLLO platform seeks to improve upon
Nancy agreed to repeat biopsies during her melanoma
this standard practice.
treatment, beyond the usual pre-treatment biopsy. Dr. Wargo is a leader of an effort to employ deep molecular and immune analysis of tumors before, during and after treatment to understand who benefits, who doesn’t and what to do next after any treatment fails.
“If you don’t get a biopsy before, during and after treatment, you aren’t going to learn about how tumors evolve and resist treatment.” — Ignacio Wistuba, M.D. Nancy Pinkston completed her immunotherapy in
“We should be incorporating this sort of biopsy and
late 2016 with no side effects from treatment. Her
blood sample analysis into clinical trials, and ultimately
experience demonstrates how the APOLLO platform is
we may even incorporate this into treatment with
leveraging a relatively new understanding of cancer —
standard-of-care therapy. This effort is critical to
that it can behave differently before, during and after
guiding patient care in this era of precision medicine,”
treatment — to find the best course of treatment for
Dr. Wargo says.
our patients. Such a comprehensive effort would not be possible without the generous support of donors.
In the next two years, APOLLO is scheduled to conduct such analyses in 2,100 patients enrolled in 28 high-
APOLLO
priority clinical trials for melanoma; multiple myeloma; glioblastoma; lymphoma; lung, breast, colorectal, pancreas and ovarian cancers; sarcoma; and cancers caused by the human papillomavirus. A solid tumor pilot study using the APOLLO approach
Genomic sequencing
Cancer Genomics Laboratory
led by Dr. Wargo found that analyzing biopsies taken early during treatment with a similar immunotherapy
23
CANCER GENOMICS LABORATORY Program Leaders: Andrew Futreal, Ph.D.; Kenna Shaw, Ph.D.
Next-generation sequencing has transformed how
that ensures data from multiple platforms are consistent
cancer is diagnosed and treated. Scientists now can
and comparable.
identify changes to the genes that control cell function, particularly genes that regulate how cells grow and
Thanks to recent technology developments, we have
divide. Because every person’s cancer is different and
implemented protocols to increase efficiency and allow
every tumor has its own unique abnormalities at the
for reliable sequencing of low-quantity and low-quality
genetic level, MD Anderson clinical researchers can
DNA/RNA samples. We are developing a targeted
Researchers analyze the gene sequence in the tumor and compare it to the same individual’s normal gene sequence. The differences identify where potential targets may lie.
determine whether a
gene panel to interrogate cell-free DNA (cfDNA) —
patient’s tumor carries
bits of DNA floating free in the bloodstream that may
clinically significant
be signposts of disease. Cell-free DNA obtained by a
mutations that make
simple blood draw would reduce the need for invasive
it vulnerable to a
and expensive biopsies. In addition, we have deployed
particular drug or
two new targeted gene sequencing panels that focus
therapy.
on specific genes or gene regions that have a known or suspected association with the cancer of interest. For
The Cancer Genomics Laboratory platform of
example, the solid tumor panel was updated to include
MD Anderson’s Moon Shots ProgramTM performs
DNA damage response genes and was co-developed
next-generation sequencing for all of the Moon Shots
with input from five Moon Shots.
and provides molecular analyses of genomic DNA and transcriptomic RNA, which has a significant impact on
Finally, we are in the last steps of implementing an
the detection, management and treatment of cancer.
immuno-oncology gene expression assay. Immunooncology seeks to answer questions about why the
Over the past year, and with your generous support,
immune system does not recognize and destroy
we have sequenced more than 3,000 samples
cancer cells. The assay, which requires minimal sample
from 11 diseases. Nearly 50% of our sequencing
input, would identify certain molecular markers that
efforts were directed at leukemia samples for the
may enable the immune system to recognize and
APOLLO platform, which tracks the mutational
stamp out tumor cells. Applications such as these
changes of cancers at strategic points throughout
are designed to address specific biological and
treatment so that we can better understand the
clinical questions that are necessary to further our
behavior of cancer cells.
understanding of cancer and propel new discoveries. These milestones could not have been reached
The resulting high-quality data then flows into the Big Data Enterprise Warehouse designed to store and allow access to that information for all MD Anderson researchers. This means cancer experts can use data created for one type of cancer that might have an impact on another type of cancer. The Cancer Genomics Laboratory serves as an essential part of the pipeline
24
without your support.
Lin-Ya Tang, coordinator, in the Cancer Genomics Laboratory
25
PROTEOMICS Program Leader: Sam Hanash, M.D., Ph.D.
The proteomics platform helps investigators identify proteins or molecules in the blood that are useful for the detection and diagnosis of cancer. The platform also helps identify new targets for cancer treatments. Lung cancer remains the top cause of cancer deaths worldwide. While smoking is the primary culprit of the disease, this statistic includes an increasing number of never-smokers as well as those who do not meet the current risk criteria to trigger CT screening for
Sam Hanash, M.D., Ph.D. Colorectal Cancer Moon Shot
lung cancer. Based on a critical need for a simpler diagnostic method, we have made significant progress in our efforts to establish a blood test for
Diagnostic blood tests
lung cancer. We have met with the FDA to present our plans for the test’s validation and are working on
Prostate Cancer Moon Shot
meeting the agency’s requirements for such a study. To date, more than 5,000 participants have enrolled in the study. As we prepare for FDA approval of this test, we are placing substantial emphasis on its clinical implementation by developing effective modalities to screen for lung cancer. For the highest-risk group, our
Proteomics Lung Cancer Moon Shot
Pancreatic Cancer Moon Shot
approach combines CT screening and a blood test. For those at intermediate risk, the strategy involves a
current therapy based on folfirinox, a chemotherapy
blood test first, followed by CT screening if that blood
regimen for treatment of advanced pancreatic cancer.
test is positive, with the goal of catching as many
We have identified a major enzyme in tumor tissue that
cases of early-stage lung cancer as possible while
activates a previously inactive drug in folfirinox, thereby
saving patients and the broader health care industry
potentiating response to this treatment.
innumerable time and money in the process. In prostate cancer, we have identified and are now
26
Last year, we expanded the proteomic platform’s
testing several early detection blood biomarkers
involvement to additional cancer types in the Moon
that can help us predict the likelihood of prostate
Shots ProgramTM, particularly those with a critical
cancer being aggressive. In parallel, we are testing
need for diagnostics. We are pleased to report that
a novel lipidomics-based model for the drivers
we have made significant progress in validating a
of early aggressive prostate cancer. Finally, we
blood test for the early detection of pancreatic cancer
identified plasma biomarkers in patients undergoing
in the preclinical setting. Another important finding
active surveillance for prostate cancer. These
pertaining to pancreatic cancer is the discovery and
accomplishments would not be possible without
validation of a marker predictive of response to the
donor support, for which we are grateful.
LUNG CANCER MOON SHOT Program Leaders: John Heymach, M.D., Ph.D.; Jack Roth, M.D.; Stephen Swisher, M.D.
Daniel Gomez, M.D.
Lung cancer is the leading cause of cancer mortality
In 2016, we developed a training program, Changing
worldwide, and smoking contributes to upwards of
Tides, to establish a national standard for certified
80% of lung cancer deaths. The Lung Cancer Moon
tobacco treatment specialists. The goal is to
Shot™ combats this disease with a multi-pronged
disseminate MD Anderson-level expertise across
approach — helping to prevent young people from
the country. Thanks to your generosity, we began
starting to smoke; helping those who currently smoke
training for the program in August 2017 and expect
to quit; detecting lung cancer early when it’s treatable;
it to reach up to 43 health care providers, generating
and effectively treating it after malignancy has
more than 1,000 hours of continuing education. We
advanced from its early phases.
want to prepare health care professionals to deliver high-intensity, evidence-based, cognitive-behavioral
A Smoking Prevention Interactive Experience (ASPIRE)
treatment for nicotine dependence — just like
is an interactive program designed to reduce risk of
the Tobacco Treatment Program offered onsite at
tobacco use among adolescents. Last year, donor
MD Anderson. Additionally, four novel Moon Shot
support helped retool ASPIRE, modernizing both the
clinical trials aim to improve delivery of quit methods
content and functionality of the program, which you
and customize treatment for nicotine addiction —
can view at mdanderson.org/aspire.
assigning each participant to the intervention most likely to work based on factors that predict treatment
27
response (behavioral, genetic and neurobiological).
several research disciplines to improve treatment
These trials are exceeding recruitment goals, and
options for all lung cancer types. The project goal is to
results are expected to change clinical practice for
find cancer-driving mutations for every subset of lung
smoking cessation.
cancer — including NSCLC and those seen in only 1 or 2% of lung cancer patients. The GEMINI database
On the detection front, oncologists typically rely on
has collected detailed molecular information on more
X-ray, CT scan and/or tissue biopsy to detect lung cancer
than 4,000 lung cancer patients over the past three
in its early stages. We need to eliminate these expensive,
years. The project supported the first randomized
invasive options while maintaining the ability to detect
lung cancer clinical trial to test the hypothesis that
the disease at a time when it is most treatable.
aggressive treatment of residual metastatic disease
To this end, we have opened an international
using surgery and/or radiation (local consolidative
clinical trial focused on detecting lung cancer
therapy, or LCT) after chemotherapy could benefit
in heavy smokers using a blood test (developed
patients with limited metastatic disease. The
through our proteomics platform) and CT imaging.
benefits were so significant that the clinical trial
The goal is to show that this cheaper, safer diagnosis
was discontinued early by the data safety review
modality is as, or more, effective at detecting
board due to early
cancer than standard methods. Recent validation
efficacy. In the past
studies have confirmed that the blood test detects
year, we have built
approximately 60% of lung cancer in patients showing
on this finding by
no signs of cancer whatsoever. With your philanthropic
combining LCT with
support, the trial already has enrolled 1,450 of the
immunotherapy and
expected 10,000 patients in sites around the world.
targeted therapies, such as those that inhibit epithelial
This study established LCT as a potential standard-of-care treatment option for a subset of lung cancer patients previously offered only chemotherapy.
growth factor receptors. Clinical trials testing these Standard-of-care practices for non-small cell lung
new therapeutic combinations are currently ongoing,
cancer (NSCLC) benefit only 50% of patients with
with early results expected in 2018. Your generosity is
NSCLC, at best. The Genomic Marker-Guided Therapy
making this possible.
Initiative (GEMINI) unites lung cancer experts across
“There’s no place where the people doing the research and the people in the clinic treating patients are working together any more closely.” — John Heymach, M.D., Ph.D.
28
PANCREATIC CANCER MOON SHOT
Program Leaders: Anirban Maitra, M.B.B.S.; Robert A. Wolff, M.D.; Matthew Katz, M.D.
This past year, with your support, the Pancreatic
have not spread past the pancreas. Each trial will be
Cancer Moon Shot™ team has made progress both
accompanied by extensive blood- and tissue-based
in the clinic and in the laboratory in our efforts to
analyses to unravel the underpinnings of response
diagnose patients earlier, increase survival after
and resistance to particular treatments.
surgical tumor removal and provide new therapies for In addition, we are collaborating with the Institute
this disease.
for Applied Cancer Science and the Center for CoMany pancreatic cancer patients with localized disease
Clinical Trials to develop targeted therapies that
will have their tumor resected (surgically removed).
inhibit recurrently abnormal genes and pathways in
Patients will live even longer, MD Anderson has
pancreatic cancer, including KRAS, which is mutated
The median overall survival for pancreatic cancer patients who successfully complete neoadjuvant therapy and surgical resection at MD Anderson is nearly double the national average.
shown, if they undergo
in as many as 95% of pancreatic cancer cases. These
neoadjuvant therapy
therapies have been shown to be highly effective
(i.e., chemotherapy with
in multiple pancreatic cancer preclinical models.
or without radiation
Several therapies will soon enter Phase I clinical trials
before surgery). Our
for pancreatic cancer, including IACS-10759, which is
goal is to evaluate novel
currently being used in an ongoing Phase I trial for
neoadjuvant treatments,
acute myeloid leukemia (for more on this trial, see
including immunotherapy,
AML-MDS Moon Shot report on page 11).
and enhance resectability and survival in our patients. This coming year, we will conduct a series
Additionally, our team is aggressively determining how
of clinical trials focused on patients whose cancers
immunotherapy can become a viable treatment option
29
for pancreatic cancer. We have successfully isolated T
sophisticated imaging techniques to pinpoint the
cells from patients, expanded them in the laboratory
location of the disease so that we can manage it
and then re-injected large volumes of these powerful
appropriately. To address this, we’re developing an
immune cells back into patients to more effectively
image processing method called enhancement pattern
fight their tumors. A new clinical trial is currently
mapping that enables detection of small-volume
enrolling patients to determine if this approach will
pancreatic tumors by amplifying abnormal signals that
generate a significant favorable response.
are usually undetectable.
Pancreatic biopsies are challenging and potentially
The chance that a healthy adult in the general
risky, but they are of extreme importance for
population will develop pancreatic cancer is
determining accurate diagnoses and prognoses for
approximately one in 10,000. However, individuals with
patients. Our novel liquid biopsy program enables
an inherited predisposition to this malignancy present
the complete genomic characterization of every
a unique opportunity for screening and early diagnosis
patient’s tumor using only a single vial of blood. This
at an asymptomatic stage. To offer this service to
technology places us in a unique position to “match”
such individuals, we’ve established Houston’s first
patients to the best trial without requiring them to
Pancreatic Cancer High-Risk Clinic, which will advise
undergo invasive tissue biopsies. This personalized
families touched by this disease, and track the
program operates in collaboration with the APOLLO
detection and progression of their disease through
platform, which means the information collected from
serial screening studies.
this study will guide drug development and allow clinicians to track a patient’s response to therapy.
We are incredibly grateful for your support, which allows us to work towards our ultimate goal of
Once a sensitive and specific blood test is available for detecting pancreatic cancer early, we’ll need
Dr. Wolff and colleagues discuss treatment strategies.
30
drastically reducing mortality from pancreatic cancer.
PROSTATE CANCER MOON SHOT Program Leaders: Christopher Logothetis, M.D.; Filippo Giancotti, M.D., Ph.D.
The leadership of the Prostate Cancer Moon ShotTM
paradigm increases effectiveness and reduces the
has prioritized projects with potential for immediate
toxicity of therapy. We are awaiting sufficient follow-up
impact on patient care. Thanks to your support,
and analysis of the data.
we have made advances in understanding why immunotherapy has not worked well in prostate
The DynAMo trial allocates patients to the most
cancer, and we are seeing promising clinical results
appropriate combination therapy based on their
in testing ways to overcome immunotherapy’s
responses to maximal hormonal therapies.
limitations. We have performed studies to classify prostate cancer into molecularly defined therapeutically relevant subgroups. We have deployed a liquid biopsy strategy that will minimize
This study is the first to take into account the heterogeneity of prostate cancer biology.
the necessity for invasive core biopsies. These
It seeks to efficiently associate marker signatures
advances have allowed us to transition from a single-
to drug response with distinct action mechanisms
agent therapy strategy to more effective combinations
that will guide future treatment strategies and the
of treatments guided by markers.
development of novel therapies within biologically informed clinical trials. Specifically, based on our
Prostate cancer is notoriously resistant to
previous studies in the clinic and in the laboratory,
immunotherapy. Based on our observations, the
men who have aggressive prostate cancers have
combined immunotherapy studies will determine if
combination chemotherapy added to the hormonal
we can overcome the limited effectiveness of single-
treatment, while men with less aggressive disease are
agent immune checkpoint inhibition with a combined
randomized to the addition of immunotherapy. As of
immune checkpoint blockade. This has evolved
now, we have 89 patients enrolled on the DynAMo
from the discovery of new immune targets to clinical
clinical trial.
applications with promising results within 18 months. We are immensely grateful for having the philanthropic We have completed the first “intent-to-cure� clinical
support to take important steps toward the conquest
trial for prostate cancer with androgen ablation (to
of this deadly disease. Without this generous funding,
reduce levels of the male hormone that fuels most
none of these advances would be possible. On behalf
prostate cancers) for selected men with early but high-
of our patients and investigators, thank you for your
risk prostate cancer. This will determine if a curative
trust in our research. 31
COLORECTAL CANCER MOON SHOT Program Leaders: Ernest Hawk, M.D.; Scott Kopetz, M.D., Ph.D.;
Amjad Talukder, Ph.D., instructor, and
Stanley Hamilton, M.D.
Greg Lizee, Ph.D., associate professor
MD Anderson’s Colorectal Cancer Moon Shot™ has
increasing in this population. In collaboration with
made substantial progress in the past year against the
the proteomics platform, we have developed
third most commonly diagnosed malignancy in both
a blood test intended to allow primary care
men and women in the U.S. Our team is focused on
doctors to screen patients for colorectal cancer
three major areas: biomarker development for early
and polyps that lead to it. This test detects
detection, molecular subtype identification to more
biomarkers — tiny indicators of colorectal polyps/
effectively treat patients and personalized vaccine
cancers — and will allow for blood-based screening
development to harness the body's immune system to
of younger patients and more targeted use of
fight the disease.
colonoscopies for diagnosis in such screen-positive individuals. For patients who have residual cancer
32
Colonoscopies are largely effective at preventing
that is nearly undetectable after curative colorectal
colon cancer. Unfortunately, their effectiveness as
surgery, we are planning clinical trials that will also
screening tools at the population level has been
use blood-based biomarkers as surveillance tools.
limited because they are expensive, invasive and
Our approach offers a “liquid biopsy” strategy for
operator-dependent and require significant planning.
earlier detection to better stratify patients for either
Because of this, colonoscopies are not always done
continued surveillance or additional treatment. For
as frequently as recommended. Furthermore, they
example, immunotherapy might be given in response
are not widely available throughout the world, nor are
to a positive liquid biopsy to prevent cancer from
younger patients currently recommended to receive
spreading to the lung — a common site of colorectal
screening, in spite of colorectal cancer incidence
cancer metastasis. Validation studies of liquid biopsy
methods are ongoing and include analysis of many thousands of patients in the U.S. and Europe. On the treatment side, scientists have observed that
We are developing a test that will help identify patients’ tumor subtypes and steer them into appropriate clinical trials.
colorectal cancers behave differently in different
On the immunotherapy front, our team completed
people. Our investigators helped identify four distinct
a pilot study of personalized vaccines that are built
colorectal cancer molecular subtypes. We are now
by molecularly defining a patient's tumor. This
strategically positioned to better understand the
study is demonstrating promising results and is
behaviors of tumors based on such molecular
moving into a new phase in which the vaccines are
subtypes. This will allow for more personalized
paired with immune checkpoint inhibitors. These
therapeutic approaches based on molecular
immunotherapies help make cancer cells visible to
categorizations, rather than treating colon cancer
immune system cells that are designed to eliminate
with a more traditional “one-size-fits-all� approach.
the tumor.
We demonstrated that classification can be useful in understanding more aggressive or more slowly
Thanks to the generosity of our donors, the Colorectal
growing disease subtypes. Our team has also
Cancer Moon Shot investigators are leading efforts
identified how the immune system behaves differently
to reduce the incidence of colorectal cancer and
depending on the molecular subtype. This knowledge
providing meaningful improvement in patient survival.
led to a series of clinical trials that target specific susceptibilities within these four distinct subgroups.
33
“Our obligations are unwavering and are not subject to the shifting strategic priorities common to the pharmaceutical industry. Our stakeholders are the patients and they deserve nothing less than our daily, passionate commitment to the development of innovative therapies.” — Carlo Toniatti, M.D., Ph.D.
ORBIT
Program Leaders: Carlo Toniatti, M.D.; Ph.D., Jeffrey Molldrem, M.D.; Michael Curran, Ph.D.
The Oncology Research for Biologics and Immunotherapy
single agent and combination therapy. Phase II clinical
Translation (ORBIT) platform is dedicated to the discovery
trials are expected to begin in 2018.
and development of anti-cancer monoclonal antibodies (mAbs) — molecules that selectively recognize specific
Another advanced program in the immune checkpoint
proteins expressed on a cell’s surface. Our goal is to
space involves an mAb that can increase T cell-
effectively guide, accelerate and execute the translation
mediated anti-tumor immune responses and synergize
of novel discoveries into anti-cancer therapeutic mAbs.
with other immunotherapies in preclinical models. ORBIT leaders feel this mAb has a high likelihood of
ORBIT is currently invested in two major areas:
becoming a safe and effective drug. We intend to find a
immune-checkpoint and T cell receptor (TCR)-
partner to start large-scale manufacturing of this mAb
like mAbs.
during 2018 with intent to enter the clinic in late 2019.
Immune-checkpoint mAbs can be used to bypass the
T cell receptor-like antibodies are a novel class of
immuno-suppressive properties of cancers and trigger
antibodies that mimic the receptor used by T cells to
a strong immune response against tumors. This class of
recognize specific targets on cancer cells and kill them.
mAbs represents the basis for the recent renaissance of
They combine the selectivity of TCRs with the strength,
cancer immunotherapy, which is producing spectacular
flexibility and pharmacologic properties of mAbs. The
results in the clinic, albeit only in a small percentage of
first ORBIT TCR-like antibody that will enter the clinic
patients and only in some cancer types. Our goal is to
is h8F4, an mAb that specifically targets and kills AML
develop novel immune checkpoint antibodies that can
cells in patients who express the PR1/HLA-A2 complex
provide a therapeutic benefit to patients that do not
on the surface of cancer cells (about 40% of the total
respond to existing immunotherapies.
AML patient population). We reached a co-development agreement with Astellas Pharma for this drug, and the
The first proprietary immune checkpoint mAb
Phase I trial of
developed at MD Anderson was an anti-OX40 agonist
this first-in-class
monoclonal antibody, which targets a protein present
mAb is projected
on the surface of T cells, thereby stimulating their anti-
to launch during
cancer activity. We entered a collaborative licensing
the first quarter
agreement with GlaxoSmithKline to co-develop this
of 2018. This is a testament to the quality of work and
mAb, the clinical development of which started in late
complexity of operations only possible at MD Anderson,
2015 and has progressed throughout 2017. Trials for
thanks to the support of our generous donors.
this drug are currently in the late stage of Phase I as
34
This will represent the only example in the world of an mAb entirely developed from target identification to Phase Ib proof-of-concept trial within an academic institution.
IMMUNOTHERAPY Program Leaders: James Allison, Ph.D.; Patrick Hwu, M.D.; Padmanee Sharma, M.D., Ph.D.
Immunotherapy is one of the newest and most
than 170 patients with AML who were undergoing
promising treatment approaches in the fight against
immunotherapy on clinical trials. The trials are showing
cancer, and one in which MD Anderson is leading the
encouraging efficacy by adding immunotherapy
way. Cancer immunotherapy has taken decades to bring
agents involving PD-1 antibodies to standard-of-
to fruition, and the immunotherapy platform has been
care hypomethylating agents, showing a doubling
the leader in bringing immunotherapy to the forefront
of response rate and improved overall survival in
as a potent weapon against cancer. Our program
frontline and relapsed AML, as well as high-risk MDS.
encompasses highly integrative basic science studies,
The immunotherapy platform is evaluating pre- and
translational research and clinical trials.
post-treatment patient samples using single-cell analyses, CyTOF and other next-generation sequencing
The strength of the immunotherapy platform is its ability to adapt based on what we learn from our clinical trials.
As we continue to
technologies. We are the first group to perform such a
expand the number
detailed analysis of ongoing clinical trials with immune
of trials, patients and
checkpoint inhibitors in AML and MDS.
samples with which we work, we are constantly
We continue to work with Moon Shots teams to bring
incorporating the newest technologies to streamline
the most advanced immunotherapies to bear on
our analyses of longitudinal samples from trials.
specific tumor types and integrate cutting-edge basic
For example, we have developed newer panels and
immunology with novel trials to gain information for
incorporated single-cell mass cytometric analyses
the treatment and eradication of cancer. We thank
for a deeper understanding of T cells and other
our generous donors for their support, without which
immune cells, which have a major impact on cancer
none of this would be possible.
progression. More than 63,000 blood and From our collaboration with the department of
tissue samples processed, covering
Leukemia and the AML-MDS Moon Shot™, we
a broad range of tumor types across
collected bone marrow and blood samples from more
18 departments from 113 clinical trials
35
GLIOBLASTOMA MOON SHOT Program Leaders: Amy Heimberger, M.D.; Frederick Lang, Jr., M.D.; John de Groot, M.D. Uncovering better treatments for glioblastoma, the most common brain tumor, is the goal of MD Anderson’s Glioblastoma Moon Shot™. Current standard regimens include surgery, radiation and
A second immunotherapy approach in
chemotherapy — harsh treatments that often mean
preclinical studies focuses on chimeric antigen
severe side effects for patients. Nevertheless, we are
receptor (CAR) T cells. Amy Heimberger,
making progress by developing more effective, patient-
M.D., professor of Neurosurgery, devised a
friendly approaches.
method to reduce the amount of time needed to produce these cells from 28 days to 14.
One promising area for treating glioblastomas
Halving the time for CAR T cell production is
is immunotherapy. Elizabeth Shpall, M.D., and
a huge win for patients who need access to
Katy Rezvani, M.D., Ph.D., professors of Stem Cell
therapy quickly.
Transplantation and Cellular Therapy, opened an exciting clinical trial targeting cytomegalovirus (CMV). Evidence indicates that most glioblastomas exhibit
type of brain cancer, a 15% response rate is incredibly
CMV-derived viral proteins. MD Anderson researchers
exciting. Second, the team noticed that the presence of
have crafted CMV-specific T cells from the peripheral
a foreign virus elicited a simultaneous immune reaction,
blood of glioblastoma patients that detect, find and
suggesting viral and immunotherapy combinations
kill the CMV-protein-producing tumor cells. Since the
may be an effective approach. In light of this, a new
trial opened, the six enrolled patients have shown no
clinical trial has opened teaming Delta-24-RGD with the
adverse effects stemming from the treatment. Once
immunotherapy pembrolizumab. Patients enrolled in
the safety studies conclude, the next step is to test the
the trial are already showing encouraging results.
tumor-killing potency of this approach in patients. Lastly, by leveraging the extensive molecular profiling Viral therapy could be the next frontier in glioblastoma
efforts of MD Anderson’s APOLLO platform, we have
treatment. MD Anderson’s Delta 24-RGD is a cancer-
treated numerous patients in clinical trials by identifying
killing therapy modified from the common cold virus.
subgroups who are eligible for targeted therapies. For
Developed by Juan Fueyo, M.D., and Candelaria
example, in one of these cohorts, every patient has
Gomez-Manzano, M.D., professor and associate
three mutations on a particular chromosome and may
professor of Neuro-Oncology, respectively, the virus
respond to a drug that targets these mutations. Although
selectively infects and kills glioblastoma cells when
this is a small patient subset, molecular database surveys
delivered directly to the tumor. Then, the Delta- 24-RGD
have identified 10
replicates within the dying tumor cell before bursting
more people who
out and flooding the tumor with copies of itself,
may be eligible for
essentially releasing a new therapy wave.
this therapy.
In a Delta-24-RGD clinical trial led by Frederick Lang,
With heartfelt appreciation, we thank you for
M.D., professor of Neurosurgery, our team made
supporting our efforts in improving the disease
two critical discoveries. First, 15% of patients treated
outcomes of patients with glioblastoma.
demonstrated a beneficial therapeutic effect. For any 36
Those 10 people will be given a better chance to beat cancer because of the unique, collaborative structure of the Moon Shots ProgramTM.
For more updates, visit: cancermoonshots.org
CANCERMOONSHOTS.ORG